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Antibiotics in Coloproctology

Compiled and edited by :.

GLIMPSES FROM HISTORY – ANTISEPSIS & ANTIBIOTICS

Antisepsis

• Earlier days- surgery followed by infection & pus –’laudable’.
• Egyptian embalmers - able to prevent putrefaction – skills of mummification.
• Hippocrates (460-377 B.C.) recognized the antiseptic properties of wine, oil, and vinegar & used in dressing of wounds.
• Microscopy - 17th century- confirmed the presence of microbes.
• Theory of spontaneous generation
• 1860-Sir Louis Pasteur -Germ theory of disease.

• Heinrich Koch (1843-1910) proved that germs cause disease. And laid down Koch’s postulates
• 1843- Ignaz Semmelweiss introduced washing of hands in an antiseptic chloride solution before examining patients.
• 1867 Sir Joseph Lister, introduced, technique and principles of antisepsis for surgery - LANCET, 1867
• 1890 - William Halsted, use of Rubber gloves in surgery .

Antibiotics.

• First systemic antiseptic - Ehrlich – arsenical named Salvarsan- effective against spirochetes-‘ Magic Bullet’
• 1929 – Sir Alexander Fleming discovered Penicillin- accidentally from a mould Pencillium notatum.
• 1935- Domagk discovered Prontosil – active ingredient – Sulfanilamide- first of Sulphonamides- effective against Gonorrhea.
• 1940s, A. Schatz and S. Waksman - Streptomycin, effective against both G -ve bacteria and Mycobacterium tuberculosis.
• 1947- Chloramphenicol was discovered.

Surgical infections.

Defn: Surgical Infections are those that

• • Present as a result of a surgical procedure – Surgical Site Infections ( SSI)
  • Require surgical intervention as part of the treatment. ( E.g. Intra abdominal abscess, acute appendicitis etc)

Characteristics of a surgical infection:

• • Result of a damaged host defense system- esp. injury to the epithelial barrier.
  • Pathogens causing infection are usually mixed – aerobic & anaerobic.
  • Pathogens are from patients own endogenous flora( Opportunistic).
  • Usually accompanies tissue necrosis.

* Primary principle when treating surgical infection is source control. (E.g. abscess drainage, closure of perforation etc,.)

* Antibiotic treatment and systemic support - only adjunctive therapies , and wont resolve surgical infection without operative Rx

Pathogens in surgical infections.

Bacteria of surgical infections are broadly divided into aerobic & facultative bacteria in one gr and anerobic bacteria in another / into Gram + ve & Gram _ve bacteria / into Bacilli & Cocci.

• Source of pathogens can be:
• endogenous or exogenous.

  But most surgical infections are caused by endogenous bacteria.

  Mostly mixed flora- aerobic & anaerobic.

  Specific bacteria found in specific parts of the body , exposed anatomic areas during procedures – source of pathogens.

Endogenous source:

• • acquired from individuals own commensals.
  • Common after trauma , surgery and instrumentation, and in lowered local or general resistance.
  • Commensal flora, not of consistent composition, is constantly changing , altered by antibiotics- broad spectrum .
  • Many commensals are potential pathogens.

• Skin & mucus membranes: skin is rich in staph epidermidis, micrococci, coryneforms and anaerobic cocci. On mucus membranes flora is predominantly anaerobic. 30% of people are carriers of Staph aureus a potential pathogen particularly in axilla, toe webs, nose.

• Gastro intestinal tract: few organisms in stomach and small intestine. Large intestine – vast microbial flora, predominantly anaerobic. Such as Bacteroides spp, Bifidobacteria and Clostridia. Also aerobes like E.coli & Enterococcus.

Exogenous source:

• Acquired from a source outside the patient. Can be from :

1. 1. Human source.
   2. Animal source

3. Environmental source: community acquired or hospital acquired

Why need to know:

• • for suspecting the possible pathogen causing infection .
  • to suspect the origin of an unknown source of infection in pts with +ve blood culture.
  • for selection of appropriate antibiotics
  • • to start intelligent empiric therapy.
    • To direct antimicrobial prophylaxis.

Antibiotics in colorectal surgery

Why & When.

• To treat established Surgical infections-Antibiotic Therapy.

• For Antibiotic Prophylaxis prior to surgery.

Antibiotic therapy

Therapy aimed at established surgical infections.

Goal of antibiotic therapy:

• To achieve a concentration of antibiotic in the infected tissue that exceeds the MIC by 3 or 4 times for at least ¾ s of the time between successive doses.

Principles of antibiotic therapy:

• • • • Choice of Antibiotics.
      • Route of administration.
      • Duration & Dose of administration.

Choice of antibiotic:

• Most surgical infections are caused by mixed bacterial flora, it is difficult to culture all these organisms and bacterial identification takes a minimum of 48 -72 hrs.

• Hence antibiotics must be started empirically and directed at the most likely pathogens.

• Gram staining & biochemical tests can help in providing earlier guidances regarding which group of causative bacteria.

1. Coverage of the presumed organisms involved should be ensured. Starting with broad spectrum drugs and narrowed down to specific organism isolated.
2. Concentration of the antibiotic that can be achieved at the site of infection.
3. Toxicity should be considered , particularly in critically ill patients in which bioavailability & therapeutic & toxic level range are harder to predict.
4. When a new antibiotic regimen is started , set a time limit for the period for which the antibiotic will be given.
5. The pathogenicity , synergism, and the antagonism exhibited by the bacteria in various mixed infections.
6. The negative effects of antibiotics with host defense mechanisms
7. The results of well controlled clinical studies of unselected patients.

• • • was the initial operative procedure adequate?
    • the initial procedure was adequate but has a complication occurred?
    • has a super infection developed at a new site?
    • The drug choice is correct, but is enough is being given?

• The choice of antibiotics is not the most common cause of failure unless the original choice was clearly inappropriate.

• Because of systemic response to infection & impaired GI function in severe surgical infections – Intravenous route is the preferred route in initial antibiotic therapy.

• After initial parenteral therapy, patient can be switched to oral antibiotics to complete the course.

• Antibiotics are usually given for too long duration & in insufficient dosages, because surgeons have problems distinguishing between contamination, infection and continuing inflammation.

• Longer duration of therapy indicated in immunocompromised Pt or when focus control is difficult.

• A reliable guideline is to continue antibiotics until Pt has shown obvious clinical improvement and has had a normal Temp for 48 hrs or more.

• Signs of improvement include improved mental status, return of bowel function, resolution of tachycardia, and spontaneous diuresis

Surgical site infections.

• Defined by: Surgical Wound Infection Task Force – 1992.

• Defn. Postoperative infections that present in any location along the surgical tract within 0 to 30 days after a surgical procedure or within 1 yr in procedures involving implants.

• SSI Classification:

• • Incisional – superficial ( skin, subcutaneous tissue)

• • Incisional – deep ( fascial planes, muscles)

• • Organ/ space related ( anatomic location of procedure) eg : intra abd abscess

• Incidence of SSI: 38%
• Most common: incisional infections : 60 -80% of SSIs.
• Organ related SSIs – 93% of SSI related mortality.

CRITERIA FOR DEFINING A SURGICAL SITE INFECTION

Superficial incisional SSI

Criterias as per Defn. + at least one of the following:

• 1. purulent drainage, with or without laboratory confirmation, from the superficial incision.
• 2. organisms isolated from an aseptically obtained culture of fluid or tissue from the superficial incision.
• 3. at least one of the following signs or symptoms of infection:

_ pain or tenderness

_ localised swelling

_ redness

_ heat

• 4.diagnosis of superficial incisional SSI by the surgeon or attending physician

Deep incisional SSI

Criterias as per defn + at least one of the following:

• 1. purulent drainage from deep incision .
• 2. a deep incision spontaneously dehisces or is deliberately opened by a surgeon when the patient has either

_ fever (>38°C)

_ localised pain or

_ tenderness

• 3. an abscess or other evidence of infection involving the deep incision is found on direct examination, during reoperation, or radiologic examination
• 4. diagnosis of deep incisional SSI by a surgeon or attending physician.
• Note: Report infection that involves both superficial and deep incision sites or an organ/space SSI that drains through the incision as deep incisional SSI.

Organ/space SSI

Criterias as per definition + at least one of the following:

• 1.purulent discharge from a drain that is placed through a stab wound into the organ/space
• 2.organisms isolated from an aseptically obtained culture of fluid or tissue in the organ/space
• 3.an abscess or other evidence of infection involving the organ/space that is found on direct examination, during reoperation, or by histopathologic or radiologic examination.
• 4.diagnosis of an organ/space SSI by a surgeon or attending physician.

Causes and Risk factors:

• • • • Bacterial factors.
      • Local wound factors.
      • Patient factors.

Bacterial factors:

• • Bacterial no., Virulence, antimicrobial resistance.
  • Wound classification:
  • Length of preoperative hospital stay.
  • Remote site infection at the time of surgery.
  • Duration of the procedure.
  • Pre operative shaving.
  • Intensive care unit patient.
  • Prior antibiotic therapy.

• Bacterial no., Virulence, antimicrobial resistance.
• • Toxins, resistance to phagocytosis, intracellular destruction.
  • Surface components ( capsules, lipopolysaccharides)
  • Bacterial load more than 105.

• Duration of the procedure:

Prolonged surgeries : > 75th percentile for that procedure.

• Preoperative shaving:
• • Increases risk by 100%.
  • Extensive shaving not needed. Removal by clippers before procedure preferred.

• • Prior antibiotic therapy : Increases chances of antibiotic resistance.

• Wound classification:

Antibiotic Prophylaxis applies to all Elective operations ( first 3 categories) and Emergency operations of the clean type. Other categories – Antibiotic Therapy.

Local wound factors.

• • Hematoma / seroma.
  • necrosis.
  • Sutures.
  • Drains.
  • Foreign bodies.

• All these factors, increase the risk of SSIs.
• Good surgical technique – best way to avoid SSIs.

Patient factors.

• • • • Comorbidities
      • Age
      • Immunosuppression
      • Malignancy
      • Obesity
      • Diabetes
      • Malnutrition.
      • Perioperative transfusions
      • Cigarette smoking
      • inspired oxygen fraction
      • Body temperature.
      • Glucose control

• Comorbidities:

American society of anaesthesiologists - Preoperative risk score ( ASA score) based on Co-morbidities.

An ASA score of > 2 , increases risk of SSI.

• inspired oxygen fraction: > 80% - ^ oxygen tension & white cell function & decreases SSIs.

• Body temperature: Normothermia reduces SSIs.

• Glucose Control: control of glucose levels in perioperative period and later upto 48 hrs reduces SSIs.

Prevention of SSIs:

Preventive measures can be:

• • Micro organism related
  • Local wound related
  • Patient related

Microorganism related.

Primary measures that have proven effective.

• • Aseptic & antiseptic technique.
  • Proper antimicrobial prophylaxis.
  • Implementation of surveillance programmes.

Aseptic and antiseptic techniques.

Environmental & architectural char. of OT.

• Size
• Air management
• Equipment handling
• Traffic rules
• Operating Room personnel asepsis and clothing.

Surgical site preparation.

• Antiseptic preoperative showers
• Skin preparation of the surgical site ( germicidal antiseptic, incise drapes)
• Scrubbing ( 1st time – 5 mins, consecutively 3 mins)
• Alcoholic hand scrub soln.
• Sterile drapes & gowns.
• Double gloving.

Preventive measures can also be classified as:

Anti microbial prophylaxis

Prophylaxis: Why?

• Hospital acquired infection , of which SSI is the commonest, costs about 170 million $ in UK
• SSI increase morbidity & mortality, Prolong hospital stay, and increase medical care cost.
• Colorectal surgery -high risk of SSI due to contamination by contents of large bowel
• Use of antimicrobial prophylaxis - reduces risk of wound infection from 40% to 11%.
• Reduces need for long term antibiotic Rx- reduces development of resistance.
• In trials of antibiotics vs No antibiotics use in colorectal surgery , the SSI rate was 12.9% vs 40.2%.

Reality check:

• UK audits :25 – 50% of all antibiotics prescribed - for prophylaxis.
• Prophylactic use is often inappropriate than therapeutic use.
• Prophylactic antibiotic use is suboptimal in 40-50% of operations.
• • lack of reliable process in the hospital.
  • Lack of understanding.

Goals of Antibiotic prophylaxis

• Reduce incidence of SSI.
• Antibiotic Use supported by evidence of effectiveness.
• Minimal effect on Pts normal bacterial flora.
• Minimal adverse effects.
• Minimal change to Pt’s host defences.

*Antibiotic prophylaxis is an adjunct to , not a substitute for good surgical technique.

Principles of antimicrobial prophylaxis

• Choice of antimicrobial agent and regimen.
• Timing and duration
• Route of administration.

Choice of antimicrobial agent

• Regimens designed should cover the entire spectrum of suspected microbes. In colorectal surgery – both aerobes & anaerobes..

• No antibiotic reliably superior than other, when each possessed similar & appropriate antibacterial spectrum.

• >70 different antibiotic regimens exist- effectiveness similar.

• • Past history of adverse event- preclude use of particular gr of antibiotics.

• • Prophylactic Antibiotics ,chosen as per local prevalence of antibiotic resistance.

• • Search for ideal prophylactic regimen – continuous process. Avoid ,Universal acceptance and use of any particular regimen

Timing and duration

• Concentration of antibiotics in the surgical wound should exceed MIC of the bacteria at the time of bacterial contamination, to prevent infection.

• Most effective when begun preoperative & continued per operative.

• First dose – within 30 mins of anesthesia induction.

• Antibiotics started as late as 3 hrs after contamination are markedly less effective.

• Single dose regimen vs multiple dose regimen- no significant difference.

• For prolonged surgeries – repeated doses at intervals of 1 or 2 half lives for the drug.

• Decision regarding multiple dose regimen should be based on other factors which increase the risk of infection, such as:

- Duration of surgery.

- Peri operative blood transfusion.

- Presence of drains.

- Immunocompromised state, etc,,.

Route of administration

• Prophylactic antibiotics for surgical procedures should be administerd intravenously.

• Oral + parenteral antibiotic prophylaxis is advocated for colorectal surgery. In RCT of Parenteral alone Vs parenteral + oral antibiotics, significant reduction in infection rate in latter group.

Antimicrobial therapy of SSI

• Difficult- resistant bacteria due to pre operative antibiotic therapy.
• Should cover specific bacteria isolated and facultative & obligate anerobic flora.
• D O C : 1. 3rd generation Cephalosporin or Quinolone + metronidazole.

2. Imipenem or expanded spectrum pencillins + b lactamase inhibitor.

3. In resistant enterobacteria or serratia – aminoglycoside & b lactam inhibitor.

• Superficial incisional: drainage only , no antibiotics.
• Deep incisional: Drainage, Control of source, Antibiotic Therapy.
• Organ/ Space SSI:

Operative , as any other sec peritonitis.

or

Non operative drainage – CT or US guided ( if abscess not associated with anastomosis.) with antibiotic therapy.

Antimicrobial drugs & their Spectrum

Pencillins.

Pencillins + B-lactamase inhibitors

Cephalosporins.

Cephalosporins…cont…

Quinolones

Aminoglycosides.

Anti anerobes.

Miscellaneous.

Antibiotic prophylaxis in Colorectal surgery.

• Antibiotic prophylaxis is Highly recommended.
• The risk of SSI following Colorectal surgery is 40 to 60 % without prophylaxis.

Preperation for elective colorectal surgery :

Condon Nichols Preperation.

Preoperative day: Oral sodium phosphate solution with or without Bisacodyl in a 1 to 2 dose regimen before administration of oral antibiotics .

+ Clear liquid diet.

+ 1 gm each of oral Neomycin & Erythromycin taken at 19, 18 and 9 hours prior to surgery.

Operative day: Completely evacuate the bowel prior to surgery.

+ Parenteral antibiotics 30 mins

prior to incision ( an Aminoglycoside or Cephalosporin like Cefotetan / Cefoxitin in combination with Clindamycin / Metronidazole.)

Benefits of Antibiotic Prophylaxis

• The benefit of antibiotic prophylaxis in terms of the incidence of SSI after elective surgery is related to the severiy of the Consequences of the SSI. ( for eg. In colon anastomosis , prophylaxis reduces mortality)
• Shortens the hospital stay.
• Faster return to normal activity.

Risks Of Prophylaxis.

• Inappropriate use of antibiotics for prophylaxis.

• Increased risk of C.difficile colitis (even single dose increases risk , however more common after prophylaxis of > 24hrs.

Final decision regarding ,benefits & risks of Prophylaxis for an individual pt will depend on:

• • Patients risk of SSI.
  • The potential severity of the consequences of SSI.
  • The effectiveness of prophylaxis in that operation.
  • The consequences of prophylaxis for that patient

( e.g. increased risk of colitis)

Antibiotic Prophylaxis : Conclusions.

• Antibiotics or antibiotics combinations should be active against both aerobic & Anaerobic bacteria .

• Administration should be timed, so that the tissue concentration of antibiotics around the wound area is sufficiently high when bacterial contamination occurs.

• Single dose regimens are as effective as multiple dose regimens and are associated with less toxicity, fewer adverse effects , lower bacterial resistance rates and lower costs.

• Universal acceptance and use of one particular regimen should be avoided.

• Guidelines for prophylaxis should be developed and regularly reviewed, locally by surgeons , microbiologists and pharmacists, taking into account local resistance profiles.
• Antibiotic prophylaxis is an adjunct to , not a substitute for good surgical technique.